(a) Field of the Invention
A phosphazene-based polymer hydrogel with chemical cross-linkings formed by radiating ultraviolet (UV) and/or mixing the polymer with a cross-linking agent and/or an enzyme, a method of preparing the same, and a use thereof are provided.
(b) Description of the Related Art
A polymer hydrogel with a chemical cross-linking has a cross-linking formed by being polymerized due to the ultraviolet (UV) irradiation in a polymer; or a chemical cross-linking formed by a Michael-addition-type reaction between thiol and acrylate, acrylamide, or vinyl sulfone groups or an enzyme, to form a network structure, so that the polymer aqueous solution turns to a gel. When a polyethylene glycol-based hydrogel, which is a representative polymer hydrogel with a chemical cross-link, was used for delivering a protein drug, the protein drug was slowly released for 12 days (J. Controlled Release 76, 11 (2001)). However, on preparing the polymer hydrogel with a cross-link, it is hard to apply as a drug or physiological material carrier, because it is not easy to control gelation behavior and the physical property of gel; and a polymer hydrogel with a chemical cross-linking requires a long time to form a gel (Biomaterials 24, 11 (2003), Biomaterials 26, 4495 (2005)).
In a temperature-sensitive polymer hydrogel, the polymer aqueous solution maintains a liquid state at a low temperature, but it turns to a gel upon increasing temperature. Such sol-gel behavior may be observed in a reverse way. The temperature-sensitive polymer hydrogel is highly evaluated as a material for delivering an implant drug because it is easy for the polymer aqueous solution to be mixed with a pharmaceutical drug; it forms a three-dimensional gel at a body temperature by simply implanting to the required area without performing a surgery; and it can slowly release a drug (Nature, 388, 860 (1997), U.S. Pat. No. 6,201,072).
The present inventors have already reported that the phosphazene-based polymers obtained by substituting dichloro phosphazene linear polymer with amino acid ester and methoxy polyethylene glycol show temperature sensitive polymer characteristics in which it is an aqueous solution state under a certain temperature, but it turns to a three-dimensional gel above the certain temperature; these temperature-sensitive phosphazene-based polymers are slowly hydrolyzed in an aqueous solution (Macromolecules 32, 2188 (1999), Macromolecules 32, 7820 (1999), Macromolecules 35, 3876 (2002), Korean Patent Nos. 259,367, and 315,630, U.S. Pat. No. 6,319,984).
However, the temperature-sensitive polymer hydrogel has insufficient gel solidity, so it has limits to apply to a hydrophilic drug carrier. The polymer hydrogel being capable of chemical cross-linking by the cross-linking agent and/or enzyme has a limit to apply as an injectable carrier for physiological active material. So, in order to improve the problems, it is required to develop a biodegradable temperature-sensitive phosphazene polymer with a chemical cross-linking which is capable of showing a sol-gel behavior depending upon the temperature change to apply as an injectable carrier for physiological active material or drug; simultaneously, which has a sufficient hydrogel solidity and controls the pore size, so as to apply to a carrier for a physiological active material and a dental material such as an implant material, a tissue material such as an artificial cartilage and so on.